SUMMARY/ABSTRACT People who live with HIV (PLWH) experience a high incidence of neurocognitive deficits and HIV- associated non-AIDS (HANA) disorders, including cardiovascular disease (CVD), metabolic dysfunction, and autonomic decline. While antiretroviral treatment (ART) has reduced AIDS-related morbidity, both the virus and the medications are associated with lipid disorders that also increase CVD risk, including dyslipidemia and lipodystrophy. Consequently, the development of effective lifestyle interventions to reduce the incidence of HIV-associated neurocognitive disorders (HAND) and decrease metabolic disorders is a high priority. Physical activity (PA) has been utilized as an effective tool to improve health in PLWH, but may not be sufficient by itself to improve lipid levels. Existing PA interventions in PLWH typically required strenuous PA and significant resources that limit feasibility for many people living with the disease. Recent work indicates that interrupting periods of sedentary behavior (SB), independent of PA, also has a significant beneficial effect on metabolic function, but SB has not been well-studied in PWLH. Mediterranean-style diets (MedDiet) are also effective at improving CVD risk factors in HIV-uninfected individuals and are reported to reduce cognitive decline in persons at risk for Alzheimer's disease, but have not been widely tested in PWLH. We recently developed a novel and personalized Short Message Service (SMS) mobile phone text messaging intervention (iSTEP) that is designed to increase moderate PA in PLWH (R21MH100968). Our objective is to expand upon this work and conduct an RCT examining the efficacy of iSTEP in combination with a mobile mHealth MedDiet intervention tailored to PLWH. 180 PLWH will be randomly assigned to a control group (n = 60), a 6-month iSTEP group with just a PA/SB intervention (n = 60), or a 6-month intervention with both PA/SB and MedDiet components (n = 60), where participants receive daily interactive SMS/MMS messages designed to increase moderate PA, reduce SB, and promote adherence to a MedDiet, including walnut consumption. PA/SB will be quantified by accelerometer, Fitbit step counts, and self-report, MedDiet adherence will be assessed by self-report (Diet History Questionnaire and weekly SMS feedback) and objective measures (polyunsaturated fatty acid levels - PUFA in blood), and we will quantify metabolic and inflammatory markers. We will also conduct a follow-up assessment 6 months after the end of the intervention (accelerometer, neurocognitive testing, PUFA levels) to assess PA and MedDiet adherence. We hypothesize that iSTEP (both intervention arms) will increase PA, reduce SB, and improve neurocognition compared to control; the iSTEP + MedDiet group will demonstrate improvement in CVD risk factors and neurocognition compared to the PA/SB intervention alone. Findings from this proposal will lay the groundwork for development of novel large-scale mobile PA/diet interventions dedicated to treating HAND and improving cardiovascular health for PLWH.